Evidence for Other Medical Therapy in Women

Although digoxin therapy has been demonstrated to decrease HF hospitalization,54 it has not been demonstrated to improve survival. In a retrospective analysis of the Digitalis Investigation Group (DIG) trial, digoxin was associated with an increased risk of death from any cause among women, but not men, with HF and reduced LVEF.55 However, that analysis did not account for serum potassium concentration and serum digoxin concentration differences. Another analysis of the same trial reported no excess mortality in either women or men with digoxin at serum concentrations between 0.5 and 0.9 mg/ml.56 This report demonstrated that digoxin levels are higher in women compared to men at any given dose presumably due to decreased lean body mass and renal function. Analysis of the Studies of Left Ventricular Dysfunction (SOLVD) trials also did not demonstrate an increase in mortality in women with digoxin.57

Although sex-specific data is not available from prospective trials on the benefits of aldosterone antagonists for women with LV systolic dysfunction and symptoms of HF, adequate numbers of women were included in the large randomized, controlled trials of these agents and subgroup analyses were shown to demonstrate benefit in women.58,59